title: Inhibition of CNS remyelination by the presence of semaphorin 3A.
abstract: Failure of oligodendrocyte precursor cell (OPC) differentiation has been recognized as the leading cause for the failure of myelin regeneration in diseases such as multiple sclerosis (MS). One explanation for the failure of OPC differentiation in MS is the presence of inhibitory molecules in demyelinated lesions. So far only a few inhibitory substrates have been identified in MS lesions. Semaphorin 3A (Sema3A), a secreted member of the semaphorin family, can act as repulsive guidance cue for neuronal and glial cells in the CNS. Recent studies suggest that Sema3A is also expressed in active MS lesions. However, the implication of Sema3A expression in MS lesions remains unclear as OPCs are commonly present in chronic demyelinated lesions. In the present study we identify Sema3A as a potent, selective, and reversible inhibitor of OPC differentiation in vitro. Furthermore, we show that administration of Sema3A into demyelinating lesions in the rat CNS results in a failure of remyelination. Our results imply an important role for Sema3A in the differentiation block occurring in MS lesions.
authors.affiliation: Anne McLaren Laboratory for Regenerative Medicine, Medical Research Council Centre for Stem Cell Biology and Regenerative Medicine, University of Cambridge, Forvie Site, Cambridge CB2 0SZ, United Kingdom.
authors.forename: Yasir A
authors.initials: YA
authors.lastname: Syed
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hand
authors.forename: Wiebke
authors.initials: W
authors.lastname: Möbius
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.forename: Matthias
authors.initials: M
authors.lastname: Hofer
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Nave
authors.forename: Mark R
authors.initials: MR
authors.lastname: Kotter
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040121:Semaphorin-3A / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D040121:Semaphorin-3A